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1.
Graefes Arch Clin Exp Ophthalmol ; 257(8): 1813, 2019 08.
Article in English | MEDLINE | ID: mdl-31165246

ABSTRACT

The article "A comparison of risk factors for age-related macular degeneration and polypoidal choroidal vasculopathy in Chinese patients" has been retracted.

2.
Biomed Res Int ; 2018: 3242574, 2018.
Article in English | MEDLINE | ID: mdl-29850504

ABSTRACT

Diabetic macular edema is major cause of vision loss associated with diabetic retinopathy. Breakdown of blood-retinal barrier, especially inner BRB, is an early event in pathogenesis of DR. Apelin, an endogenous ligand of APJ, mediates angiogenesis and is involved in the development of DR. The present study aimed to investigate effects and mechanism of apelin-13 in vascular permeability during DME. We verified apelin-13 was upregulated in DME patients' vitreous. High glucose incubation led to a progressive increase of apelin-13, APJ, cytoskeleton, and tight junction proteins, including VE-Cadherin, FAK, Src, ZO-1, and occludin. Apelin-13 promoted HRMEC proliferation and migration and phosphorylation of both cytoskeleton and tight junction under both normal and high glucose conditions. Besides, apelin-13 activated PI-3K/Akt and MAPK/Erk signaling pathways, including PLCγ1, p38, Akt, and Erk both in HRMEC and in C57BL/6 mice. Meanwhile, F13A performed opposite effects compared with apelin-13. In in vivo study, apelin-13 was also upregulated in retina of db/db mice. Taken together, apelin-13 increased biologic activity of HRMEC, as well as expression of both cytoskeleton and tight junction in DME via PI-3K/Akt and MAPK/Erk signaling pathways. Apelin-13 as an early promoter of vascular permeability may offer a new perspective strategy in early treatment of DR.


Subject(s)
Apelin/pharmacology , Cytoskeleton/metabolism , Diabetic Retinopathy/pathology , MAP Kinase Signaling System/drug effects , Macular Edema/pathology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Tight Junctions/metabolism , Adult , Aged , Animals , Apelin Receptors/antagonists & inhibitors , Apelin Receptors/metabolism , Capillary Permeability/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , Cytoskeleton/drug effects , Diabetic Retinopathy/enzymology , Epithelial Cells/drug effects , Epithelial Cells/enzymology , Epithelial Cells/metabolism , Female , Glucose/toxicity , Humans , Intercellular Signaling Peptides and Proteins/pharmacology , Macular Edema/enzymology , Male , Mice, Inbred C57BL , Middle Aged , Phosphorylation/drug effects , Tight Junctions/drug effects , Vitreous Body/drug effects , Vitreous Body/metabolism
3.
Graefes Arch Clin Exp Ophthalmol ; 256(8): 1449-1457, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29858677

ABSTRACT

PURPOSE: Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) are important vision-threatening diseases worldwide. For effective treatment, the risk factors for the diseases merit investigation. This study aimed to compare the risk factors for nAMD vs. PCV in Chinese patients. METHODS: A total of 946 participants were recruited in this case-control study, including 281 patients with nAMD, 306 patients with PCV, and 359 controls. All participants underwent comprehensive ophthalmic examinations. Information on risk factors were collected by questionnaire. Multivariate logistic regression analyses were performed to investigate the difference in risk factors between nAMD and PCV. In a subgroup of subjects, serum lipid data were obtained and analyzed. RESULTS: Risk factors for nAMD included older age (OR 1.03, P = 0.001), male gender (OR 1.55, P = 0.020), asthma (OR 2.50, P = 0.028), smoking (OR 1.92, P = 0.001), and family history (OR 6.82, P = 0.001), while smoking (OR 1.67, P = 0.013) was the only risk factor for PCV. Compared to patients with PCV, patients with nAMD were more likely to be older and suffer from hyperlipidemia, coronary artery disease, rheumatism, and tumor. Interestingly, higher levels of high-density lipoprotein were positively associated with PCV in the subgroup analysis (OR 7.74, P = 0.011). Besides, results were quite different between the combination of patients with nAMD and PCV and patients with nAMD or PCV alone. CONCLUSIONS: The risk factors for nAMD and PCV is varying with the exception of smoking. Our findings suggest that different strategies might be applied in the clinical management and scientific research on nAMD and PCV.


Subject(s)
Choroid Diseases/epidemiology , Choroid/blood supply , Macula Lutea/pathology , Macular Degeneration/epidemiology , Polyps/epidemiology , Risk Assessment , Adult , Aged , Aged, 80 and over , China/epidemiology , Choroid Diseases/diagnosis , Female , Fluorescein Angiography , Fundus Oculi , Humans , Incidence , Macular Degeneration/diagnosis , Male , Middle Aged , Polyps/diagnosis , Prognosis , Retrospective Studies , Risk Factors , Tomography, Optical Coherence
4.
Int J Clin Exp Pathol ; 10(11): 10711-10729, 2017.
Article in English | MEDLINE | ID: mdl-31966415

ABSTRACT

Diabetic retinopathy is major cause of vision loss during working age. Breakdown of blood-retinal barrier is an early event in pathogenesis of DR. RPE is the major part of outer BRB. Apelin, an endogenous ligand of APJ, mediates angiogenesis. Our previous study showed that apelin induced proliferation, migration, and collagen I mRNA expression in human RPE cells via PI-3K/Akt and MAPK/Erk signaling pathways. Now we investigate the connection between apelin and RPE in vascular permeability of diabetic retinopathy and its working mechanism. Our study showed that apelin promotes the proliferation, migration and expression of cytoskeleton and tight junction proteins in human RPE cells using MTS and transwell chamber assay. Apelin also activated the expression of PI-3K/Akt and MAPK/Erk signaling pathways proteins, such as PLCγ1, p38, Akt and Erk phosphorylation in RPE cells using laser scanning confocal detection, PCR and western blot. Pretreatment with the inhibitor of apelin receptor APJ, F13A, abolished the apelin-induced activations of the proliferation, migration and expression of cytoskeleton, tight junction and PI-3K/Akt and MAPK/Erk signaling pathways proteins in human RPE cells. It suggested that apelin as a promoter in retinal vascular permeability during early stage of DR, provides further evidence for neurovascular crosstalk in pathogenesis of DR, which may offer a new target in early prevention and treatment of DR.

5.
Mediators Inflamm ; 2016: 7920631, 2016.
Article in English | MEDLINE | ID: mdl-27378826

ABSTRACT

Background. Epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) is vital in proliferative vitreoretinopathy (PVR) development. Apoptosis-stimulating proteins of p53 (ASPP2) have recently been reported to participate in EMT. However, the role of ASPP2 in PVR pathogenesis has not been identified. Methods. Immunohistochemistry was used to investigate the expression of ASPP2 in epiretinal membranes of PVR patients. ARPE-19 cells were transfected with ASPP2-siRNA, followed with measurement of cell cytotoxicity, proliferation, and migration ability. EMT markers and related inflammatory and fibrosis cytokines were measured by western blot or flow cytometry. Additionally, PVR rat models were induced by intravitreal injection of ARPE-19 cells transfected with ASPP2-siRNA and evaluated accordingly. Results. Immunofluorescence analysis revealed less intense expression of ASPP2 in PVR membranes. ASPP2 knockdown facilitated the proliferation and migration of RPE cells and enhanced the expression of mesenchymal markers such as alpha smooth muscle actin, fibronectin, and ZEB1. Meanwhile, ASPP2-siRNA increased EMT-related and inflammatory cytokines, including TGF-ß, CTGF, VEGF, TNF-α, and interleukins. PVR severities were more pronounced in the rat models with ASPP2-siRNA treatment. Conclusions. ASPP2 knockdown promoted EMT of ARPE-19 cells in vitro and exacerbated the progression of experimental PVR in vivo, possibly via inflammatory and fibrosis cytokines.


Subject(s)
Apoptosis Regulatory Proteins/genetics , RNA, Small Interfering/metabolism , Vitreoretinopathy, Proliferative/genetics , Vitreoretinopathy, Proliferative/metabolism , Adult , Aged , Apoptosis/genetics , Apoptosis/physiology , Blotting, Western , Cell Line , Cell Movement/genetics , Cell Movement/physiology , Cell Proliferation/genetics , Cell Proliferation/physiology , Female , Humans , Immunohistochemistry , In Vitro Techniques , Male , Middle Aged , RNA, Small Interfering/genetics , Retina/metabolism , Retina/pathology , Reverse Transcriptase Polymerase Chain Reaction , Vitreoretinopathy, Proliferative/pathology , Young Adult
6.
Chin Med J (Engl) ; 128(18): 2505-9, 2015 Sep 20.
Article in English | MEDLINE | ID: mdl-26365970

ABSTRACT

BACKGROUND: This study was to examine the expression of total vascular endothelial growth factor (VEGF) and the anti-angiogenic VEGF 165 b isoform in the vitreous body of retinopathy of prematurity (ROP) patients, and to further study the role of the VEGF splicing in the development of ROP. METHODS: This was a prospective clinical laboratory investigation study. All patients enrolled received standard ophthalmic examination with stage 4 ROP that required vitrectomy to collect the vitreous samples. The control samples were from congenital cataract patients. The expression of total VEGF and the anti-angiogenic VEGF 165 b were measured by enzyme-linked immunosorbent assay. Results were analyzed statistically using nonparametric tests. RESULTS: The total VEGF level was markedly elevated in ROP samples while VEGF 165 b was markedly decreased compared to control group. The relative protein expression level of VEGF 165 b isoform was significantly decreased in ROP patients which were correlated with the ischemia-induced neovascularization. CONCLUSIONS: There was a switch of VEGF splicing from anti-angiogenic to pro-angiogenic family in ROP patients. A specific inhibitor that more selectively targets VEGF 165 and controls the VEGF splicing between pro- and anti-angiogenic families might be a more effective therapy for ROP.


Subject(s)
Protein Isoforms/metabolism , Retinopathy of Prematurity/metabolism , Vascular Endothelial Growth Factor A/metabolism , Vitreous Body/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Humans , Infant, Newborn , Infant, Premature , Male , Prospective Studies
7.
Nat Commun ; 6: 6687, 2015 Apr 15.
Article in English | MEDLINE | ID: mdl-25872646

ABSTRACT

Age-related macular degeneration (AMD) is a leading cause of irreversible central blindness among the elderly worldwide. We use exome sequencing to analyse nonsynonymous single-nucleotide variants (SNVs) across the whole genome of 216 neovascular AMD cases and 1,553 controls. As a follow-up validation, we evaluate 3,772 neovascular AMD cases and 6,942 controls from five independent cohorts in the East Asian population. Here we show strong evidence of an association at a novel, missense SNV, rs7739323, which is located in the ubiquitin protein ligase E3D (UBE3D) gene (Pmeta=1.46 × 10(-9), odds ratio (OR)=0.74, 95% confidence interval (CI): 0.63-0.88). Furthermore, ablation of the UBE3D protein lead to an abnormal amount of pigment granules deposited in retinal pigment epithelium microvilli area and an abnormal response on electroretinography (ERG) in UBE3D(+/-) heterozygous mice. Our findings indicate that the ubiquitin-proteasome system may play a role in the pathogenesis of neovascular AMD.


Subject(s)
Asian People/genetics , Macular Degeneration/genetics , Ubiquitin-Protein Ligases/genetics , Aged , Angiography , Animals , Case-Control Studies , China , Coloring Agents , Electroretinography , Exome/genetics , Female , Genetic Predisposition to Disease , Hong Kong , Humans , Indocyanine Green , Japan , Macular Degeneration/pathology , Male , Mice , Mice, Knockout , Middle Aged , Polymorphism, Single Nucleotide , Retinal Pigment Epithelium/pathology , Sequence Analysis, DNA , Singapore , Tomography, Optical Coherence
8.
World J Pediatr ; 10(3): 262-70, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25124978

ABSTRACT

BACKGROUND: Clinical trials have revealed that the antivascular endothelial growth factor (VEGF) therapies are effective in retinopathy of prematurity (ROP). But the low level of VEGF was necessary as a survival signal in healthy conditions, and endogenous placental growth factor (PIGF) is redundant for development. The purpose of this study was to elucidate the PIGF expression under hypoxia as well as the influence of anti-VEGF therapy on PIGF. METHODS: CoCl2-induced hypoxic human umbilical vein endothelial cells (HUVECs) were used for an in vitro study, and oxygen-induced retinopathy (OIR) mice models were used for an in vivo study. The expression patterns of PIGF under hypoxic conditions and the influence of anti-VEGF therapy on PIGF were evaluated by quantitative reverse transcription-polymerase chain reaction (RTPCR). The retinal avascular areas and neovascularization (NV) areas of anti-VEGF, anti-PIGF and combination treatments were calculated. Retina PIGF concentration was evaluated by ELISA after treatment. The vasoactive effects of exogenous PIGF on HUVECs were investigated by proliferation and migration studies. RESULTS: PIGF mRNA expression was reduced by hypoxia in OIR mice, in HUVECs under hypoxia and anti-VEGF treatment. However, PIGF expression was reversed by anti-VEGF therapy in the OIR model and in HUVECs under hypoxia. Exogenous PIGF significantly inhibited HUVECs proliferation and migration under normal conditions, but it stimulated cell proliferation and migration under hypoxia. Anti-PIGF treatment was effective for neovascular tufts in OIR mice (P<0.05). CONCLUSION: The finding that PIGF expression is iatrogenically up-regulated by anti-VEGF therapy provides a consideration to combine it with anti-PIGF therapy.


Subject(s)
Endothelial Cells/drug effects , Hypoxia/metabolism , Pregnancy Proteins/drug effects , Retinopathy of Prematurity/prevention & control , Vascular Endothelial Growth Factors/antagonists & inhibitors , Animals , Animals, Newborn , Disease Models, Animal , Endothelial Cells/metabolism , Female , Humans , In Vitro Techniques , Infant, Newborn , Mice , Mice, Inbred C57BL , Placenta Growth Factor , Pregnancy Proteins/metabolism , Retina/metabolism , Retina/pathology , Retinopathy of Prematurity/metabolism , Umbilical Veins , Up-Regulation
9.
Ophthalmic Res ; 50(3): 180-6, 2013.
Article in English | MEDLINE | ID: mdl-24008241

ABSTRACT

AIMS: To investigate the expression of placental growth factor (PIGF) in alkali burn-induced murine corneal neovascularization (NV); to evaluate the effects of KH902, a vascular endothelial growth factor receptor decoy, on prevention and regression of new vessels growths in the cornea; and to determine the influence of KH902 on the levels of vascular endothelial growth factor (VEGF) and PIGF in alkali burn-induced corneal NV. METHODS: Mouse corneal NV was induced by alkali burn. The expression of PIGF was detected by immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR). To evaluate the effects of KH902, corneal NV was observed and photographed every 3 days for a total of 28 days after the alkali burn. The percentage of NV area was measured and compared with that of the control group. The VEGF and PIGF levels in the cornea were evaluated by enzyme linked immunosorbent assay (ELISA). RESULTS: PIGF was expressed during the alkali burn-induced corneal neovascularization. On day 3 (D3), day 6 (D6) and day 9 (D9) after chemical cauterization, the length of the longest new vessel and the neovascularization areas in the KH902-treated groups were significantly smaller than those of the PBS-treated group (p < 0.05). The areas of established corneal NV of the KH902-treated groups regressed with time, but the control groups showed no natural regression. The VEGF and PIGF levels of the cornea in the treated groups were significantly decreased compared to those of the control group (p < 0.05). CONCLUSIONS: PIGF may be involved in alkali burn-induced corneal NV. KH902 significantly inhibited new vessel growth and promoted the regression of established vessels in a mouse model of corneal NV, and it also reduced the levels of VEGF and PIGF in the cornea.


Subject(s)
Burns, Chemical/complications , Corneal Neovascularization/drug therapy , Eye Burns/chemically induced , Pregnancy Proteins/metabolism , Recombinant Fusion Proteins/therapeutic use , Animals , Burns, Chemical/metabolism , Cornea/drug effects , Corneal Neovascularization/chemically induced , Corneal Neovascularization/metabolism , Disease Models, Animal , Eye Burns/complications , Eye Burns/metabolism , Immunohistochemistry , Male , Mice , Mice, Inbred C57BL , Placenta Growth Factor , Recombinant Fusion Proteins/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Vascular Endothelial Growth Factor A/metabolism
10.
Article in English | MEDLINE | ID: mdl-23737827

ABSTRACT

Therapeutic interventions in prediabetes are important in the primary prevention of type 2 diabetes (T2D) and its chronic complications. However, little is known about the pharmacogenetic effect of traditional herbs on prediabetes treatment. A total of 194 impaired glucose tolerance (IGT) subjects were treated with traditional hypoglycemic herbs (Tianqi Jiangtang) for 12 months in this study. DNA samples were genotyped for 184 mutations in 34 genes involved in drug metabolism or transportation. Multinomial logistic regression analysis indicated that rs1142345 (A > G) in the thiopurine S-methyltransferase (TPMT) gene was significantly associated with the hypoglycemic effect of the drug (P = 0.001, FDR P = 0.043). The "G" allele frequencies of rs1142345 in the healthy (subjects reverted from IGT to normal glucose tolerance), maintenance (subjects still had IGT), and deterioration (subjects progressed from IGT to T2D) groups were 0.094, 0.214, and 0.542, respectively. Binary logistic regression analysis indicated that rs1142345 was also significantly associated with the hypoglycemic effect of the drug between the healthy and maintenance groups (P = 0.027, OR = 4.828) and between the healthy and deterioration groups (P = 0.001, OR = 7.811). Therefore, rs1142345 was associated with the clinical effect of traditional hypoglycemic herbs. Results also suggested that TPMT was probably involved in the pharmacological mechanisms of T2D.

11.
J Ocul Pharmacol Ther ; 29(7): 619-26, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23545016

ABSTRACT

PURPOSE: Pathological retinal angiogenesis is a major cause of vision loss. Endostatin is a natural antiangiogenesis antitumor protein that is widely used in cancer studies. In this study, we investigated the efficacy and potential mechanisms of endostatin for the prevention of retinal neovascularization both in vitro and in vivo. METHODS: Human umbilical vein endothelial cells (HUVECs) were used for the in vitro studies. HUVECs were incubated with endostatin or the vascular endothelial growth factor (VEGF) and endostatin for different time points. Cell proliferation, migration, cell cycling, and tube formation studies were carried out using a Cell Counting Kit-8 assay, a Transwell assay, flow cytometry, and a Matrigel assay, respectively. Enzyme-Linked Immunosorbent Assay (ELISA) was used to study VEGF and pigment epithelial-derived factor (PEDF) protein secretion from the HUVECs at different time points. A murine oxygen-induced retinopathy (OIR) model was used for the in vivo studies. Seven-day-old C57BL/6J pups (p7) were exposed to 75% oxygen for 5 days. On p12, the animals were returned to a normal atmosphere and were immediately injected intravitreously with 1.5 µL of a 5 mg/mL endostatin solution. At p18, the mice were perfused with fluorescein-dextran-FITC, and their retinas were flat mounted to measure the nonperfused area. Retinal VEGF and PEDF levels were also measured by ELISA Kits in the OIR mice at p18. RESULTS: In vitro, endostatin inhibited HUVEC proliferation in a dose-dependent manner and also inhibited HUVEC proliferation in a VEGF-containing medium. Additionally, endostatin can inhibit migration, tube formation, and VEGF secretion in HUVECs, while also inducing apoptosis in HUVECs at several time points. These effects were statistically significant when compared to the control group (P<0.05). In vivo, a single intravitreous injection of endostatin reduced the retinal nonperfused area from 30% in the control group to 23% in the treatment group (P<0.0001). Intravitrous injection of endostatin reduced VEGF levels in retinas, while it increased PEDF levels. CONCLUSIONS: Endostatin showed convincing inhibitory effects on angiogenesis both in vitro and in vivo. The inhibitory effects may be, at least partly, resulted from the restoration of the PEDF/VEGF ratio. These data suggest that endostatin could offer an innovative pharmaceutical strategy for the prevention of retinal neovascularization.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Disease Models, Animal , Endostatins/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Oxygen/toxicity , Retinal Neovascularization/drug therapy , Retinopathy of Prematurity/drug therapy , Animals , Animals, Newborn , Apoptosis/drug effects , Blotting, Western , Cell Movement/drug effects , Cell Proliferation/drug effects , Dextrans , Enzyme-Linked Immunosorbent Assay , Eye Proteins/metabolism , Female , Flow Cytometry , Fluoresceins , Humans , Mice , Mice, Inbred C57BL , Nerve Growth Factors/metabolism , Retinal Neovascularization/metabolism , Retinal Neovascularization/pathology , Retinopathy of Prematurity/etiology , Retinopathy of Prematurity/pathology , Serpins/metabolism , Vascular Endothelial Growth Factor A/metabolism
12.
Chin Med J (Engl) ; 125(8): 1429-33, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22613648

ABSTRACT

BACKGROUND: Trabeculectomy has become a mainstream treatment in intraocular pressure (IOP) reduction for primary angle-closure glaucoma (PACG); combined trabeculectomy and cataract surgery was reported to reduce IOP and simultaneously improve vision for patients with PACG and coexisting cataract. This study was specialized to compare the efficacy and safety of combined phacotrabeculectomy with that of trabeculectomy only in the treatment of PACG with coexisting cataract. METHODS: This is a comparative case series study. Thirty-one patients (31 eyes) with PACG and coexisting cataract were enrolled. Of these, 17 underwent phacotrabeculectomy and 14 underwent trabeculectomy alone. IOP, filtering blebs, and complications were compared at the final follow-up. Complete success was defined as a final IOP less than 21 mmHg without IOP-lowering medication. RESULTS: After 10 months of postoperative follow-up, the phacotrabeculectomy and trabeculectomy groups showed no significant differences regarding IOP reduction ((20.59 ± 7.94) vs. (24.85 ± 14.39) mmHg, P = 0.614), complete success rate (88% vs. 71%, P = 0.370), formation rate of functioning blebs (65% (11/17) vs. 93% (13/14), P = 0.094), and complications (41% (7/17) vs. 57% (8/14), P = 0.380). IOP-lowering medication was not required for most of the patients in both groups. Additional surgery interventions, including anterior chamber reformation and phacoemulsification, were needed in the trabeculectomy group, whereas no surgery was needed postoperatively in the phacotrabeculectomy group. CONCLUSION: Phacotrabeculectomy and trabeculectomy treatments exhibit similar IOP reduction, successful rates, and complications when it comes to treating PACG patients with coexisting cataract, although additional surgery intervention may be needed for a few cases with cataract and complications after trabeculectomy.


Subject(s)
Glaucoma, Angle-Closure/surgery , Phacoemulsification/methods , Trabeculectomy/methods , Aged , Cataract Extraction , Female , Glaucoma, Angle-Closure/physiopathology , Humans , Intraocular Pressure , Male , Middle Aged , Phacoemulsification/adverse effects , Postoperative Complications/etiology , Trabeculectomy/adverse effects , Visual Acuity
13.
J Pharmacol Exp Ther ; 342(1): 131-9, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22495066

ABSTRACT

Pathological retinal neovascularization and choroidal neovascularization are major causes of vision loss in a variety of clinical conditions, such as retinopathy of prematurity, age-related macular degeneration, and diabetic retinopathy. Pigment epithelial-derived factor (PEDF) has been found to be the most potent natural, endogenous inhibitor of neovascularization, but its application is restricted because of its instability and short half-life. Polyethylene glycol (PEG) has been used as a drug carrier to slow clearance rate for decades. The present study investigated PEGylated-PEDF for the first time and evaluated its long-term effects on preventing angiogenesis in vitro and in vivo. PEG showed lower cytotoxicity to human umbilical vein endothelial cells (HUVECs). In vitro, PEGylated-PEDF inhibited HUVEC proliferation, migration, tube formation, and vascular endothelium growth factor secretion and induced HUVEC apoptosis in a dose-dependent manner, and it showed a statistically significant difference compared with the PEDF treatment group. In vivo, PEGylated-PEDF had a long-lasting effect in both plasma and retinal concentrations. In an oxygen-induced retinopathy model, one intravitreous injection of PEGylated-PEDF after mouse pups were moved into room air resulted in a significant difference in the inhibition of retinal neovascularization, which decreased the nonperfusion area, compared with the PEDF-treated group. Our present study demonstrated for the first time the long-term inhibitory effects of PEGylated-PEDF on the prevention of neovascularization in vitro and in vivo. These data suggest that PEGylated-PEDF could offer an innovative therapeutic strategy for preventing retinal neovascularization.


Subject(s)
Eye Proteins/administration & dosage , Nerve Growth Factors/administration & dosage , Polyethylene Glycols/administration & dosage , Recombinant Proteins/administration & dosage , Retina/drug effects , Retinal Neovascularization/drug therapy , Serpins/administration & dosage , Animals , Apoptosis/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , Choroidal Neovascularization/metabolism , Choroidal Neovascularization/prevention & control , Eye Proteins/genetics , Eye Proteins/metabolism , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Mice , Mice, Inbred C57BL , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/prevention & control , Nerve Growth Factors/genetics , Nerve Growth Factors/metabolism , Rats , Rats, Wistar , Recombinant Proteins/blood , Recombinant Proteins/genetics , Retina/metabolism , Retina/pathology , Retinal Neovascularization/metabolism , Serpins/genetics , Serpins/metabolism , Vascular Endothelial Growth Factor A/metabolism
14.
Mol Vis ; 17: 2495-506, 2011.
Article in English | MEDLINE | ID: mdl-21976960

ABSTRACT

PURPOSE: To investigate the efficacy, safety, and mechanisms of Sirolimus sustained delivery film on prevention of scar formation in a rabbit model of glaucoma filtration surgery. METHODS: Sixty-four New Zealand white rabbits who underwent trabeculectomy in the right eye were randomly allocated to one of the four treatment regimens: Sirolimus sustained delivery film treatment group (Group A), or drug-free film treatment group (Group B), or 30 ng/ml Sirolimus-soaked sponge treatment group (Group C), or no adjunctive treatment group (Group D), and each group consists of 16 rabbits. Intraocular pressure (IOP), morphologic changes of bleb, anterior chamber flare, and corneal endothelial cell count and complications were evaluated over a 28-day period follow-up time. Aqueous humor samples were gathered from Group A, and the concentration of Sirolimus was measured regularly post-operation. Rabbits were sacrificed on the 7th, 14th, and 28th day post-operation separately, and the fibroblast hypertrophy, infiltration of inflammatory, and proliferation of new collagen fiber formation in each group were evaluated with HE and Masson staining. Proliferative cell nuclear antigen (PCNA) and fibroblast apoptosis were evaluated by immunohistochemistry and terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL) assay at the 28th day post-operation. RESULTS: Both Sirolimus sustained delivery film (Group A) and Sirolimus alone (Group C) were well tolerated in this model, and significantly prolonged bleb survival compared with no drug treatment group (Group B and D; p<0.001). Group A had the longest bleb survival time in comparison with other groups (p<0.001). There were significant differences in IOP readings between Group A and other groups at the last follow-up (p<0.05). The concentration of Group A maintained stable for over 2 weeks, drops from (10.56 ±0.05) ng/ml at day 3 to (7.74 ±0.05) ng/ml at day 14. The number of corneal endothelial cells of Group A was not statistically significant between pre and post-operation. Histologic examination demonstrated that eyes treated with Sirolimus, especially the Sirolimus sustained delivery film, showed an obvious reduction in subconjunctival fibroblast scar tissue formation compared with no drug treatment groups, and had minimal evidence of inflammatory cell infiltration and new collagen deposition in the subconjunctiva. Immunohistochemistry assay showed that PCNA-expression was lower in the Group A (16.25±3.24%) compared to other groups (p<0.01). TUNEL assay showed a significant increase in the number of apoptotic fibroblasts around the surgical area in Group A and Group C (9.75±1.71% and 8.50±1.92%) compared to the Group B and D (p<0.01). CONCLUSIONS: Sirolimus drug sustained delivery film can inhibit inflammatory cell activity, impede fibroblast proliferation activity, and induce fibroblast apoptosis in the filtration surgery sites in rabbit. The results indicate a safe and effective treatment strategy in anti-scaring treatment in glaucoma surgery.


Subject(s)
Apoptosis/drug effects , Cell Proliferation/drug effects , Cicatrix/prevention & control , Eye/pathology , Fibroblasts/drug effects , Filtering Surgery , Glaucoma/drug therapy , Sirolimus , Animals , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/therapeutic use , Aqueous Humor/chemistry , Blister/metabolism , Cicatrix/drug therapy , Cicatrix/pathology , Drug Administration Routes , Drug Administration Schedule , Drug Delivery Systems/methods , Endothelial Cells/cytology , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Eye/drug effects , Eye/metabolism , Female , Fibroblasts/cytology , Glaucoma/metabolism , Glaucoma/pathology , Glaucoma/surgery , Intraocular Pressure , Proliferating Cell Nuclear Antigen/analysis , Rabbits , Sirolimus/pharmacokinetics , Sirolimus/therapeutic use , Tonometry, Ocular , Trabeculectomy
15.
Mol Vis ; 17: 1449-56, 2011.
Article in English | MEDLINE | ID: mdl-21677793

ABSTRACT

PURPOSE: To investigate the genotype and phenotype of juvenile-onset open angle glaucoma (JOAG) in a Chinese family (PN pedigree). METHODS: Each family member was comprehensively examined by an experienced ophthalmologist. The clinical characteristics of the family patients with JOAG were documented. Blood samples were obtained from 22 available participants from the PN pedigree. Linkage analysis was performed to identify the possible chromosome loci. The presence of gene mutation was ascertained by polymerase chain reaction amplification and subsequent direct sequencing. RESULTS: The affected members in the PN pedigree are characterized by early age of onset (mean age at diagnosis is 17 years old), severe clinical presentations, high intraocular pressure (mean IOP of 34.18±2.97 mmHg), and poor response to pharmacological treatment (87.5% of the patients required filtering surgery). The region on chromosome 1 between D1S3464 and D1S1619 was identified in this pedigree by linkage analysis. A Pro370Leu myocilin mutation resulting from a heterozygous C→T transition at the 1,109th nucleotide in exon 3 was detected by gene sequencing. The Pro370Leu mutation co-segregated among all affected individuals of PN pedigree. CONCLUSIONS: The GLC1A Pro370Leu mutation is firmly correlated with a severe POAG phenotype. These data provide clues for the severe disease-causing nature of the Pro370Leu allele. Gene screening may be a useful method for pre-symptom diagnosis and a forewarning to detect the at-risk individuals in familial open-angle glaucoma patients, especially in pedigrees of early-onset.


Subject(s)
Asian People/genetics , Cytoskeletal Proteins/genetics , Eye Proteins/genetics , Genetic Association Studies , Glaucoma, Open-Angle/genetics , Glycoproteins/genetics , Ocular Hypertension/genetics , Adolescent , Adult , Age of Onset , Base Sequence , Child , Chromosomes, Human, Pair 1/chemistry , Female , Genetic Linkage , Genetic Loci , Genetic Testing , Genotype , Glaucoma, Open-Angle/complications , Glaucoma, Open-Angle/diagnosis , Glaucoma, Open-Angle/surgery , Heterozygote , Humans , Male , Molecular Sequence Data , Mutation , Ocular Hypertension/complications , Ocular Hypertension/diagnosis , Pedigree , Phenotype , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Tomography, Optical Coherence , Visual Acuity
16.
Chin Med J (Engl) ; 124(8): 1128-33, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21542984

ABSTRACT

BACKGROUND: Ahmed glaucoma valves (AGV) has been used for decades, but there is no detailed report about the efficacy of AGV in Chinese glaucoma patients. This study aimed to compare the intraocular pressure (IOP) lowering efficacy and side effects of S-2 polypropylene and PF-7 silicone AGV implantation in Chinese refractory glaucoma patients. METHODS: Patients were divided into S-2 model AGV group and FP-7 model AGV group. The complete and qualified surgical success rate, change of IOP, number of anti-glaucoma medications used and postoperative complications were recorded and analyzed. RESULTS: Average follow-up time was comparable between two groups. IOP was reduced from (37.9 ± 12.7) mmHg preoperatively to (17.3 ± 5.3) mmHg at the last follow-up in S-2 group and reduced from (39.9 ± 14.4) mmHg to (17.7 ± 4.9) mmHg in FP-7 group. Anti-glaucoma medications were reduced from 3.8 ± 0.2 to 1.5 ± 0.2 in S-2 group, and 3.5 ± 0.2 to 0.7 ± 0.2 in FP-7 groups. The cumulative success rates were comparable in two groups, which were 61.2% and 72.1% in S-2 group and FP-7 group respectively. When IOP reduction criteria was used, complete success rates were 30.6% and 51.2% for S-2 and FP-7 groups, and qualified success rates were 86.1% and 92.7% separately. In both groups, the major complication was hypotony, and the previous trabeculectomy of patients was the major risk factor for surgery failure. CONCLUSIONS: In this short-term retrospective study, S-2 AGV is showed at least as effective as FP-7 AGV in IOP reduction, but associated with higher rate of complications. Previous trabeculectomy is a principle risk factor for AGV implantation failure. These clinical outcomes are important for converting use of the FP-7 silicon AGV in Chinese refractory glaucoma patients.


Subject(s)
Glaucoma Drainage Implants , Glaucoma/therapy , Adult , Female , Glaucoma/physiopathology , Humans , Intraocular Pressure/physiology , Male , Retrospective Studies
17.
Chin Med J (Engl) ; 124(8): 1270-4, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21543011

ABSTRACT

Glaucoma is rarely complicated by retinitis pigmentosa (RP). To provide clinical evidences for this rare situation, we report the concurrence of these two diseases in two children of a Chinese family. In the present two-child Chinese family without positive history, the older sister presented with bilateral sector RP and coexisting chronic angle-closure glaucoma, and the brother with bilateral whole RP but without coexisting glaucoma. Clinical evidences in concurrence of variants of RP and glaucoma because of possible different gene mutations from the same genetic background represent a rare situation, which may provide clues for future researches in molecular pathogenesis of these rare diseases.


Subject(s)
Glaucoma/diagnosis , Retinitis Pigmentosa/diagnosis , Female , Humans , Young Adult
18.
Zhonghua Yi Xue Za Zhi ; 91(7): 433-5, 2011 Feb 22.
Article in Chinese | MEDLINE | ID: mdl-21418969
19.
Zhonghua Yan Ke Za Zhi ; 47(10): 893-7, 2011 Oct.
Article in Chinese | MEDLINE | ID: mdl-22321498

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of FP-7 Ahmed glaucoma valves (AGV) implantation in neurovascular glaucoma (NVG) as the first choice of surgery. METHODS: This retrospective, comparative case series study collected a total of 36 eyes of 36 patients with neurovascular glaucoma who underwent AGV implantation in Zhongshan Ophthalmic Center from January 2009 to June 2010. Change of intraocular pressure (IOP), the best corrected visual acuity, numbers of anti-glaucoma medication, success rate and postoperative complications were followed up at day 1, week 1, month 1, and every 3 months after surgery. Complete success of surgery was rated as reduction of IOP ≥ 30% without medication and those who failed to meet criteria was rated as partial success. Data were analyzed by paired Student t-test for IOP, rank sum test for paired non-parametric numbers of medication, and repeated measures analysis of variance for comparison of IOP between different time points using SPSS 13.0. RESULTS: Compared with pre-operation, IOP was significant (F = 9.26, P < 0.05) decreased after surgery with FP-7 AGV implantation (39.5 ± 9.7) mm Hg (1 mm Hg = 0.133 kPa) vs (9.2 ± 8.9), (11.8 ± 3.8), (13.7 ± 4.8), (16.9 ± 5.3), (16.9 ± 6.8) mm Hg at day 1, week 1, month 1, month 3 and the last following-up of post-operation, respectively. The numbers of anti-glaucoma medication were significantly (Z = 6.764, P < 0.05) reduced from 4.0 (1-6) of pre-operation to 1.0 (1-3) of post-operation. At the last following up, the complete success rate after FP-7 AGV implantation was 80.6%, and qualified success rate was 91.7%. The postoperative complications including occlusion of the drainage tube, exposure of the drainage tube, shallow anterior chamber and encapsulated cystic blebs around the plate were controlled with additional treatment. CONCLUSIONS: The clinical outcome indicated that the implantation of FP-7 AGV has a stable IOP lowering effect and fewer complications, which can be considered as one of the first choices for management of NVG.


Subject(s)
Glaucoma Drainage Implants , Glaucoma, Neovascular/surgery , Prosthesis Implantation/methods , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
20.
Molecules ; 15(5): 3356-65, 2010 May 07.
Article in English | MEDLINE | ID: mdl-20657485

ABSTRACT

Allergies are highly complex disorders with clinical manifestations ranging from mild oral, gastrointestinal, recurrent wheezing, and cutaneous symptoms to life-threatening systemic conditions. The levels of arachidonic acid, eicosanoids, histamine, organic acids and valine are considered to have a variety of physiological functions in connection with allergies. In this research, we have developed a RP-LC/MS method to separate and quantitate six different potential endogenous biomarkers, including leukotriene B(4) (LTB(4)), prostaglandin D(2) (PGD(2)), arachidonic acid (AA), histamine (HI), lactic acid (LA) and valine (VAL), from serum of rats with ovalbumin (OVA)-induced allergy and normal rats, and the discrepancies between the model group and the control group were compared. The separation was performed on a Prevail C18 column (250 mm x 4.6 mm, 5 microm) with a gradient elution of acetonitrile with 0.1% formic acid (v/v) and 10 mM ammonium formate (adjusted to pH 4.0 with formic acid) at a flow rate of 0.5 mL min(-1) The method was validated and shown to be sensitive, accurate (recovery values 76.16-92.57%) and precise (RSD < 10% for all compounds) with a linear range over several orders of magnitude. The method was successfully applied to rat serum and shown to be indicative of the endogenous levels of biomarkers within the rat body. The analysis of the biomarkers can provide insight into the allergic mechanisms associated with related diseases.


Subject(s)
Hypersensitivity/diagnosis , Mass Spectrometry/methods , Animals , Arachidonic Acid/blood , Biomarkers/blood , Chromatography, Liquid/methods , Histamine/blood , Hypersensitivity/blood , Hypersensitivity/etiology , Lactic Acid/blood , Leukotriene B4/blood , Mass Spectrometry/standards , Ovalbumin , Prostaglandin D2/blood , Rats , Sensitivity and Specificity , Valine/blood
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